IL149636A

IL149636A - Methods of blocking an ethylene response in plants using cyclopropene derivatives

Info

Publication number: IL149636A
Application number: IL149636A
Authority: IL
Original assignee: Univ North Carolina State
Priority date: 1999-11-23
Filing date: 2002-05-14
Publication date: 2008-11-26
Also published as: BR0015750A; WO2001037663A3; DE60008578D1; CA2391304A1; MXPA02005122A; DE60008578T2; CN1450859A; PT1233669E; DK1233669T3; EP1233669B1; KR20020059773A; JP2003533972A; AU777916B2; ES2214337T3; CN1450859B; EP1233669A2; NZ519036A; AU1784901A; TWI224494B; IL149636A0

Abstract

Methods of applying C5-20 cyclopropene derivatives and compositions thereof to block ethylene receptors in plants are disclosed. One such method comprises applying to the plant an effective ethylene response-inhibiting amount of cyclopropene derivatives or compositions thereof. Also disclosed are methods of inhibiting abscission in plants, methods of prolonging the life of cut flowers, methods of inhibiting ripening of picked fruits, and methods of inhibiting ripening of picked vegetables.

Description

149636/2 METHODS OF BLOCKING AN ETHYLENE RESPONSE IN PLANTS USING CYCLOPROPENE DERIVATIVES This invention was made with government support under Grant No. US-2786-96R awarded by the U.S. Department of Agriculture. The government has certain rights in the invention.

Field of the Invention The present invention generally relates to methods of blocking ethylene responses in plants and plant materials, and particularly relates to methods of inhibiting various ethylene responses including plant maturation and degradation by applying cyclopropene derivatives and compositions thereof to plants.

Background of the Invention Ethylene is known to mediate a variety of growth phenomena in plants. corresp. to IL 29492 See generally Fritz et al. U.S. Pat. No. 3,879,188. This activity is understood to be achieved through a specific ethylene receptor in plants. Many compounds other than ethylene interact' with this receptor; some mimic the action of ethylene; others prevent ethylene from binding and thereby counteract its action.

Many compounds that block the action of ethylene do so by binding to the ethylene binding site. Unfortunately, they often diffuse from the binding site over a period of several hours. See E. Sisler and C. Wood, Plant Growth Reg. 7, 181-191 (1988). These compounds may be used to counteract ethylene action. A problem with such compounds, however, is that exposure must be continuous if the effect is to last for more than a few hours.

Photoaffinity labeling has been used in biological studies to label binding sites in a permanent manner: usually by generating a carbene or nitrene intermediate. Such intermediates are very reactive and react rapidly and indiscriminately with many things. A compound already bound, however, would react mostly with the binding site. In a preliminary study, it was shown that transcyclooctene was an effective blocking agent for ethylene binding. 149636/3 3 cyclopropene derivative or a composition thereof.

AJso disclosed is a method of prolonging the life of a cut flower, comprising applying to the cut flower an effective life-prolonging amount of a cyclopropene derivative or a composition thereof.

Also disclosed is a method of inhibiting the ripening of a picked fruit, comprising applying to the picked fruit an effective inhibiting amount of a cyclopropene derivative or a composition thereof.

Also disclosed is a method of inhibiting the ripening of a picked vegetable, comprising applying to the picked vegetable an effective inhibiting amount of a cyclopropene derivative or a composition thereof.

The methods described herein may be carried out in a number of suitable manners, such as by contacting the plant with a cyclopropene derivative or a composition thereof, whether in solid, liquid, or gaseous form, or by introducing the plant, cut flower, picked fruit or picked vegetable Into an atmosphere infused with the cyclopropene derivative or a composition thereof. These and other suitable methods of application are discussed in' detail below.

Also disclosed is the use of a cyclopropene derivative as described herein for the preparation of an agricultural composition for carrying out any of the methods described above.

Detailed Description of the Invention A method of inhibiting an ethylene response in a plant, comprising applying to the plant an effective ethylene response-inhibiting amount of a compound of Formula I: wherein: n is a number from l to 4; and each R is independently a saturated or unsaturated, linear or branched-chain, unsubstituted or substituted, C6 to C alkyl, alkenyl, or aikynyl. interpreted broadly and may include compounds in which one or more of the carbons in one or more of the R groups is replaced by a group such as ester groups, nitriles, amines, amine salts, acids, acid salts, esters of acids, hydroxyl groups, halogen groups, and heteroatoms selected from the group consisting of oxygen and nitrogen or where such chains include halogen, amino, alkoxy, carboxy, alkoxycarbonyl, oxycarbonylalkyl, or hydroxy substituents. Thus, the resulting R groups can contain, for example, hydroxyl, ether, ketone, aldehyde, ester, acid, acid salt, amine, amine salt, amide, oxime, nitrile, and halogen groups.

Cyclopropene derivatives which may be used to carry out the present bromide with base gives the cyclopropene (see Binger, P.; Synthesis 974, 190).

Cyclopropene can be deprotonated with a strong base such as sodium amide in liquid ammonia and alkylated with an alkyl halide or other alkylating agent to give a substituted cyclopropene (reference: Schipperijn, A. J.; Smael, P.; Reel. Trav. Chim. Pays-Bas, 1973, 92, 1159). The lithium salt of substituted cyclopropenes, generated from the cyclopropene or by reaction of the tribromocyclopropane with an alkyllithium, can be alkylated to give new cyclopropene derivatives.

Compounds according to the present invention can also be obtained H3C(H2C)7 - — — (C Oxalyl chloride The addition of a diazo compound to an acetylene is another method that can be used for the synthesis of cyclopropenes (Mueller, P.; Cranisher, C; Helv. Chim. Acta 1993, 76, 521). Alternatively, the commercially available ethyl diazo acetate can be added to the acetylene to give the compound: glycol, butyl carbitol acetate and glycerine.

Mixtures of water and organic solvents, either as solutions or emulsions, can also be employed as inert carriers for the active compounds.

The active compounds of the present invention may also include adjuvants or carriers such as talc, pyrophyllite, synthetic fine silica, attapuigus clay (attaclay), kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite, fuller's earth, cottonseed hulls, wheat flour, soybean flour pumice, tripoli, wood flour, walnut shell flour, redwood flour and lignin.

It may be desirable to incorporate a wetting agent in the compositions commerc a y ava a e rom o ount Ol ve, J , sorbtan sesquioleate, polyethylene glycol ester of tall oil acids, sodium octyl phenoxyethoxyethyl sulfate, polyoxyethylene (20) sorbitan monolaurate (Tween® 20, commercially available from ICI Americas Inc. of Wilmington, Deleware) tris (polyoxyethylene) sorbitan monostearate (Tween® 60, commercially available from ICI Americas Inc. of Wilmington, Deleware), and sodium dihexyl sulfosuccinate.

The solid, liquid, and gaseous formulations can be prepared by various conventional procedures. Thus, the active ingredient, in finely divided form if a solid, may be tumbled together with finely divided solid carrier.

Alternatively, the active ingredient in liquid form, including mixtures, solutions, example.

The term "plant" is used in a generic sense herein, and includes woody-stemmed plants such as trees and shrubs. Plants to be treated by the methods described herein include whole plants and any portions thereof, such as field crops, potted plants, cut flowers (stems and flowers), and harvested fruits and vegetables.

Plants treated with the compounds and by the methods of the present invention are preferably treated with a non-phytotoxic amount of the active compound.

The present invention can be employed to modify a variety of different ethylene responses. Ethylene responses may be initiated by either exogenous or endogenous sources of ethylene. Ethylene responses include, for example, the ripening and/or senescence of flowers, fruits and vegetables, oleracea), arid cabbage (Brassica Olera'ceaJ, Paribus roots^ cK as potatoes (Solarium tuberosum) and carrots (Daucus), bulbs, such as onions (Allium sp.), herbs, such as basil (Ocimum basilicum), oregano (Origanum vulgare), dill (Anethum graveolens), as well as soybean (Glycine max), lima beans (Phaseolus limensis), peas (Lathyrus spp.), corn (Zea mays), broccoli (Brassica oleracea italica), cauliflower (Brassica oleracea botrytis), and asparagus (Asparagus officinalis).

Methods according to embodiments of the present invention inhibit the ripening of fruits. As used herein, "fruit ripening" includes the ripening of fruit while still on the fruit-bearing plant as well as the ripening of fruit after having been picked from the fruit-bearing plant. Fruits which may be treated by the method of the present invention to inhibit ripening include tomatoes (Lycopersicon esculentum), apples (Malus domestica), bananas (Musa sapientum), pears (Pyrus communis), papaya (Carica papaya), mangoes (Mangifera indica), peaches (Prunus persica), apricots (Prunus armeniaca), (4fstoemeri^ (Aquilegia sp.), aralia (e.g., Aralia chinensis), aster (e.g., Aster carolinianus), bougainvillea (Bougainvillea sp.), camellia (Camellia sp.), bellflower (Campanula sp.), cockscomb (celosia sp.), falsecypress (Chamaecyparis sp.), chrysanthemum (Chrysanthemum sp.), clematis (Clematis sp.), cyclamen (Cyclamen sp.), freesia (e.g., Freesia refracta), and orchids of the family Orchidaceae.

Plants which may be treated by the method of the present invention to inhibit abscission of foliage, flowers and fruit include cotton (Gossypium spp.), apples, pears, cherries (Prunus avium), pecans (Carva illinoensis), grapes (Vitis vinifera), olives (e.g. Vitis vinifera and Olea europaea), coffee (Coffea arabica), snapbeans (Phaseolus vulgaris), and weeping fig (ficus benjamina), as well as dormant seedlings such as various fruit trees including apple, ornamental plants, shrubbery, and tree seedlings. In addition, shrubbery which may be treated according to the present invention to inhibit abscission of foliage include privet (Ligustrum sp.), photinea (Photinia sp.), holly (Ilex sp.), ferns of the family Po/ypod/aceaef schefflera (Schefflera sp.), aglaonema (Aglaonema spj, cotoneaster fCotoheastersp.), barberry (Berberis sp.), w (Acacia sp.) and bromeliades of the family Brome Zaceae. £ r - ; ! " · · ; Active compounds of the present invention have proven to be unexpectedly potent inhibitors of ethylene action on plants, fruits and vegetables, even when applied at low concentrations. Among otherthings, compounds of the present invention may result in a longer period of insensitivity to ethylene than compounds found in the prior art. This longer period of insensitivity may occur even when compounds of the present invention are applied at a lower concentration than previous compounds.

The present invention is explained in greater detail in the following non-limiting Examples. In these examples, μΐ means microliters; ml means milliliters; nl means nanoliters; I means liters; cm means centimeters; and temperatures are given in degrees Celsius.

COMPARATIVE EXAMPLE A Activity of Short-Chain Cyciopropene Derivatives To obtain the minimum concentration that protected bananas from 333 μΙ/Ι of ethylene, compounds described in U.S. Patent No. 5,518,988 to Sisier et al. were applied to bananas according to the methods setforth herein. A known amount of an active compound was injected as a gas into a 3-liter jar containing a banana. The jar was sealed and the banana was removed after 24 hours. At the end of exposure, the banana was treated with 333 μΙ/Ι of ethylene in a 3-liter jar for 12-15 hours. It was then observed for ripening. The minimum concentration is the minimum concentration that protected the ?-< ^\'& ?A*Q ; .ί¾ΐΕ¾ί¾ϊ£· V- :A ir. ¾¾k:-¾, - ^\¾ -W ..·;..· · Table A Minimum Concentration and Time of Insensitivity for 1-Cyclopropenes Described in U.S. Patent No. 5,518,988 to Sisler et al.

Compound Structure Concentration Time (nl/l) (days) cyclopropene (CP) 0.7 12 Δ 1 -met 0.7 12 1 -eth 4 12 1 -propylcyclopropene Λ 6 12 (1-PCP) . CH2 ■CH2CH3 without effect when applied alone on a banana contained in a 3-liter jar. The jar was sealed and the banana was removed after 4 hours of exposure. At -the end of exposure, the banana was treated with 333 μΙ/Ι of ethylene in a 3- liter jar for 12-15 hours. It was then observed for ripening. The minimum concentration is the concentration that protected the bananas from 333 μΙ/Ι of ethylene. Ten microliters/liter of ethylene is usually considered to be a saturating amount. This procedure was repeated for 8-, 24- and 48-hour treatment times to determine the minimum concentration of active compounds of the present invention needed to provide protection from 333 μΙ/Ι of ethylene for a given treatment time. The results are shown in Table 1.

Table 1 Treatment Time and Minimum Concentration of 1-Cyclopropenes of the Present Invention on Banana Fruit Table 2 Minimum Concentration and Time of Insensitivity for 1-Cyc!opropenes Provided by the Present Invention Active Compound Structure Concentration Time (nl/l) (days) 1-h 0.4 20 1-o 0.3 25 EXAMPLES 3 THROUGH 29 In general, all cycldpropenes are stored at -80 C. All reactions were carried out under an atmosphere of nitrogen. Flash chromatography of cyclopropenes was carried out under an atmosphere of nitrogen. All target compounds were 80% or greater purity unless otherwise noted. 61.8 g of t e desred .N'-dibenzy- . . '. '-tetramet ye yene ammonum dibromide, a white solid mp 230-232°C. in ? v:^ ; 1 EXAMPLE 4 Preparation of 1-Hexyl-cyclopropene (Compound 1 ) a. 2-Bromo-oct-1-ene A solution of 9.42 ml (0.0728 mol) of 2,3-dibromopropene in 70 ml diethylether was placed under a nitrogen atmosphere by use of a Firestone valve. While cooling in an ice water bath, a solution of 0.091 mol of pentylmagnesium bromide in 70 ml diethyl ether was added slowly via addition funnel. After stirring for 2 hours while warming to room temperature, there was then added via syringe 50 ml of 1 N hydrochloric acid to the reaction cooling in an ice water bath. The resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was dried over MgS04 and filtered. The solvent was removed from the filtrate in : vacuo to yield 15.0„ g (85.7% of theory) of .81% pure 2-brpmo-oct-1-ene as an (0.00835 mol) of 1.4M methyl lithium in diethyl ether was added slowly by syringe. After 15 minutes, 2 ml of water was added via syringe. The resulting mixture was transferred to a separator/ funnel and the phases were separated. The organic layer was dried over MgS04 and filtered. The solvent was removed from the filtrate in vacuo with a bath temperature under 20 °C to yield 0.300 g (87% of theoretical) of 1-hexyl-cyclopropene pure as an oil.

EXAMPLE 5 Preparation of 3-Octylcyclopropene (Compound 2) 1-Bromo-dec-1-ene was prepared by the method of Millar et al (Millar, J. G.; Underhill, E. W.; J. Org. Chem. 1986, 51, 4726). This olefin was converted to 3-octylcyclopropene in a similar manner to the preparation of 70% pure 1-hexylcyclopropene.

EXAMPLE 6 Preparation of 1-(7-Methoxyheptyl)-cyclopropene 6-Bromohexyl methyl ether was prepared from 1 ,6-dibromohexane. To converted to 1-hexylcyclopropene.

EXAMPLE 7 Preparation of 1-(Undec-5-ynl)-cyclopropene (Compound 4) 1-Bromodec-4-yne was prepared from 1-chlorodec-4-yne. The 1- chlorodec-4-yne (10.6 g, 61 mmol) and 25 g of lithium bromide were refluxed in 80 ml of THF for 21 hours. The conversion was 74%. Ether was added, the reaction mixture was washed with water (2X) and brine, dried over magnesium sulfate and stripped. The product was dissolved in 70 ml of THF and refluxed for 8 hours with an additional 25 g of lithium bromide. This gave 95% conversion of the chloride to the bromide. The same workup provided 11.36 g of 1 -bromodec-4-yne.

The 1-bromodec-4-yne was converted to the Grignard reagent in THF. The Grignard reagent was converted to 1-(undec-5-ynl)-cycIopropene in the same manner that pentylmagnesium bromide was converted to 1- hexylcyclopropene. b. 9-(1 -Ethoxyethoxy)-2-bromonon-1 -ene A slurry of 5.6 g of magnesium turnings (230 mmol) in 00 ml of THF was treated with a small amount of 1 ,2-dibromoethane. 1-(1-Ethoxyethoxy)-6- bromohexane (38.5 g, 152 mmol) was fed slowly to the reaction mixture, maintaining the temperature at 40-50°C. At the end of the addition the reaction mixture was held 20 minutes, then transferred by cannula to solution of 33.4 g (167 mmol) of 1 ,2-dibromoprop-2-ene in 25 ml of THF at 0°C. The 5 reaction mixture was stirred at 0°C for 15 minutes, then stirred at room temperature for 15 minutes, then quenched with water. The reaction mixture was transferred into a separatory funnel. A small amount of 1 N HCI was added, the phases were separated, the ether phase was washed with water and brine, then dried over magnesium sulfate, filtered, and stripped to give 10 33.63 g of a yellow liquid which was used without further purification. c. 1 ,1 ,2-Tribromb-2-(7-hydroxyheptyl)cyclopropane ..... A mixture of 9-(1-ethoxyethoxy)-2-bromonon-1-ene (33.63g, 115 mmol), 4.1 g of N,N'-dibenzyl-N,N,N',N%tetraethylethylenediammonium dibromide, 42 g of 45% potassium hydroxide (337 mmol), 93 g of bromoform -(368 mmol) and 280 g of methylene chloride were rapidly stirred at room temperature for two days. 'When the reaction stalled, the reaction mixture was transferred to a separator funnel and washed with water. The c-20 methylene chloride phase was transferred to a flask and treated with the , ; ra pale yellow liquid.- -; ,v b-¾ ¾ w t w svjfr!w- «rr*":' .^.-n .::■■'·= ' .-. i' t i d. 1 -(7-Hydroxyheptyl)-cycloprppene . .. . ... . . , · ■ ' ' (2.5 mmol) in 25 ml of ether was treated at -78 °C with 7.2 ml of methyllithium (1.4 , 10 mmol). After 5 minutes, the reaction mixture was warmed to 0°C and held at this temperature. The reaction was quenched with saturated ammonium chloride. The reaction mixture was washed with water and brine, dried over magnesium sulfate, filtered and stripped to give 240 mg of 1-(7- 5 hydroxyheptyl)-cyclopropene (90% purity).

EXAMPLE 9 Preparation of 1-(7-Acetoxyheptyl)-cyclopropene {Compound 6) A solution of 2.5 mmol of 1-(7-hydroxyheptyl)-cyclopropene in 5 ml of ether was cooled in an ice bath. Triethylarnine (0.44 ml) and 0.21 g (2.7 mmol) of acetyl chloride were added, and the reaction mixture was stirred 1 hour at 5°C. Additional acetyl chloride (0.11 g), ether and triethylarnine were added, and the reaction was stirred at 5°C until GC analysis indicated 95% conversion. The reaction was worked up by adding more ether and washing was extracted three times with 1 N NaOH solution. A little sodium bisulfite 5 was added. The aqueous extracfs were extracted ;. ,,. with ether twice. The ether extracts were washed with brine., dried over . . magnesium, sulfate and stripped to give 0.56 g 7-(1,1 ,2-tribromo-cyclopropyl)- . '" ' 20 " heptanoic acid. b. 7-Cycloprop-1-enyl-heptanoic acid: 1 ,1 ,2-Tribromo-2-(7-carboxyheptyl)-cyclopropane (1.28 g, 3.1 mmol) was dissolved in 60 ml of ether and cooled to -78°C. Methyllithium (9.0 ml, 12.6 mmol) was added and the reaction was stirred at -78°C for two hours. The reaction mixture was put in an ice bath for 5 minutes, then recooled to - 78°C until workup. Water was added to the reaction mixture, which was warmed to room temperature. The aqueous phase was separated, and the ether phase was extracted with three times with 1 NaOH solution. The combined aqueous extracts were acidified with aqueous HCI, and extracted with ether three times. The ether extracts were washed with brine, dried over magnesium sulfate and stripped to give 300 mg of 7-cycloprop-1-enyl- heptanoic acid.

Example 11 Preparation of 7-Cycloprop-1-enyl-heptanoic acid isopropylamine salt (Compound 8) A solution of 7-cycloprop-1-enyl-heptanoic acid ethyl ester in 5 ml of ether was treated with 0.1 g of isopropyl amine at room temperature. The solvent was stripped to give '40 mg of 7-'cycl0prop-1-ienyl-heptan0ic acid - isopropylamine salt.1 - : ^**'- Γ:-·'^- ^'*1 ·ί"" ^:·· ··' - ·': -" : : ; v ii ! ·.< ■ : ■?■; ■: Α: ¾ tr : i - vw EXAMPLE 12 — — : '?ν ; — ·Γ'- ' A solution of 220 mg (1.3 mmol) of 1-(7-carboxyheptyl)-cyclopropene in ether was cooled to 0°C. Triethylamine (0.20 g, 2 mmol) was added, then 0.12 g (1.3 mmol) of methylchloroformate was added. After 2 hours at 0°C, the reaction mixture was transferred to a separatory funnel. The ether phase was washed with water (2X) and brine, dried over magnesium sulfate, filtered and stripped. The product was dissolved in ethanol, cooled in an ice bath and treated with 1 ml of a 21 % sodium ethoxide in ethanol solution. The reaction mixture was stirred ½ hour, then water and ether were added. The ether phase was washed with 1 N sodium hydroxide solution, water, and brine, dried over magnesium sulfate, filtered and stripped to give 10 mg of 75% pure 7- cycloprop-1-enyl-heptanoic acid ethyl ester.

EXAMPLE 13 Preparation of 1-(7-Cyanoheptyl)-cyclopropene (Compound 10) a. 1-(7- ethanesulfonyloxyheptyl)-cyclopropene A. solution of 3.8 mmol of 1-(7-hydroxyheptyl)-cyclopropene in 50 ml of ether was cooled in an ice bath. Triethylamtne (1 ml) and 0.4.8 g of methanesulfonyl chloride (4.2 mmol) were added and the reaction mixture was stirred for 2 ½ hours at 0°C. The reaction mixture was washed with water and brine, dried over magnesium sulfate, filtered and stripped to give 1- EXAMPLE 14 Preparation of 1-(7-N,N-Diethylaminoheptyi)-cyclopropene (Compound 11 ) a. 1 ,1 ,2-Tribromo-2-(7- N,N-diethylaminoheptyl)-cyclopropane A solution of 1.5 g of 1 ,1,2-Tribromo-2-(7-hydroxyheptyl)cyclopropane (3.8 mmol) in 10 ml of ether was cooled in an ice bath and treated with 0.77 g (6 mmol) of diisopropylethyl amine. Trifiic anhydride (1.18 g, 4.2 mmol) was added dropwise, and the reaction was stirred at 0°C for ½ hour. Excess diethylamine (roughly 4 ml) was added and the reaction was stirred overnight. The reaction mixture was quenched with water and transferred to a separatory funnel. A small amount of 1N NaOH was added. The aqueous phase was separated, the organic phase was washed twice more with water, then extracted three times with 1N HCI. The acidic washes were treated made basic with aqueous sodium hydroxide solution and extracted three times with ether. The ether was washed with brine, dried over potassium carbonate and stripped. The product was chromatographed through Florisil to give 1 ,1 ,2-tribromo-2-(7- N,N-diethylaminoheptyl)-cyclopropane. b. 1-(7-N,N-Diethylamin0heptyl)-cyclopropene ' To a solution of 1.0 g (2.4 mmol) of 1 , 1 ,2-tribromo-2-(7- N , N-diethylaminoheptyl)-cyclopropahe in 25 ml of THF at -78°C was added 4.55 ml (1.6 M, 7.3 mmol) of n-BuLi. The reaction mixture was stirred ½ hour, then quenched With methanol. The reaction mixture was warmed to room temperature. Ether was added, the organic phase was washed with water (3x) and brine, dried over magnesium sulfate, and filtered. The solution was stripped on a rotary evaporator with no heat added. A few pipetfuis of toluene were added, and the sample was stripped again to give 1-(7-fs|,N-diethyiaminoheptyl -cyclopropene.

EXAMPLE 15 Preparation of 1-(7-N,N,-Diethylammoniumheptyl)-cyclopropene acetate (Compound 12) A solution of 1-(7-N,N,-diethylamminoheptyl)-cyclopropene in ether was treated with acetic acid. The solvent was removed to give the salt.

EXAMPLE 16 Preparation of 1-(7-N,N,N-Diethylmethylammoniumheptyl)-cyclopropene iodide (Compound 13) A mixture of roughly 1.6 mmol of 1-(7-N,N-diethylaminoheptyl)- cycloprppene and excess iodomethane (roughly ½ ml in 5 ml of acetonitrile were stirred at room temperature for two hours. The reaction mixture was stripped to give 300 mg of 1-(7-N,N,N-diethylmethylammoniumheptyl)- cyclopropene iodide. ^ ^ - ^: n-. ) v.... EXAMPLE 17 · ■ :■; . b. 1,1 ,2-Tribromo-2-(hexyloxymethyl)cyclopropane A mixture of 5.9 g of 2-bromo-3-hexyloxypropene(26.7 mmol), 2.05 g of N,N'-dibenzyl-ethane-1 ,2-bis-(diethylamrnonium bromide), 10.5 g of 45% potassium hydroxide (84 mmol), 23.3 g of bromoform (92 mmol) and 70 g of methylene chloride were rapidly stirred at room temperature for two days. When the reaction stalled, the reaction mixture was transferred to a separatory funnel and washed with water. The methylene chloride phase was transferred to a flask and treated with the same amount of the phase transfer catalyst and 45% potassium hydroxide, then stirred at room temperature for an additional 3 days. The workup-recharge sequence was repeated once more, and the reaction was stirred one more day at room temperature. The reaction mixture was washed with water, the methylene chloride phase was dried with magnesium sulfate, and then stripped. The product was chromatographed on silica gel with 20% ethyl acetate 80% hexane to give 1.35 g of 87% pure 1,1 ,2-tribromo-2-(hexyloxymethyl)cyclopropane. c. 1-Hexyloxymethyl-cyclopropene A solution of 1.15 g of 1,1 ,2-tribromo-2-(hexyloxymethyl)cyclopropane (2.9 mmol) in 6 ml of ether was treated at -78°C with 1.4 ml of methyllithium (1.4 , 8.8 :mmol). Γ After 5 minutes the reaction mixture was warmed to 0°C and held. at this temperature. The reaction was quenched with saturated ammonium chloride. The reaction mixture was washed with water and brine, dried oyer magnesium sulfate, filtered and stripped to give 320 mg of 1- hexylo^methyl-cyGlopropenei:as a dark yellow liquid. r¾¾ ?v.,¾v ^EXAMPLE 18 . . -..; ..· ,.y; ., a. " Preparation of 2-Bromo ^ent ldkybutene : ; - 1· To a three neck round bottom flask equipped with an addition funnel and an overhead stirrer was added 35 ml of hexane, 42 g of 50% sodium hydroxide and 0.50 g of tetra-n-butylammonium bromide. A mixture of 10 g of 2-bromobuten-4-ol (66 mmol) and 15 g (100 mmol) of 2,3-dibromopropene were fed to the well-stirred reaction mixture. When the addition was complete, the reaction mixture was warmed to for 1 hour, then water was added, and the phases were separated. The organic phase was washed with water and brine, dried over magnesium sulfate, filtered and stripped. A column was run (silica gel, 20% ethyl acetate/80% hexane) to give product that was 70% pure. The more volatile material was removed by distillation under reduced pressure; the material left in the pot was 1.63 g of 99% pure 2-bromo-4-pentyloxybutene.

This olefin was converted to 1-pentyloxyethyl-cyclopropene in the same manner that 2-bromo-3-hexyloxypropene was converted to 1-hexyloxymethyl-cyclopropene.

EXAMPLE 19 Preparation of 3,3-Dipentyl-cyclopropene (Compound 16) a. 2-Pentyl-hept-1 -ene b. 2,2-Dibromo-1 ,1 -dipentyl-cyclopropane To a solution of 4.16 g (0.0247 mol) of 2-pentyl-hept-1-ene in 31 ml of pentanes, was added 4.95 g (0.0441 mol) of potassium t-butoxide. While cooling the resulting mixture to an internal temperature of 5°C, 4.01 ml ( 0.0459 mol) of bromoform was added slowly via addition funnel. The reaction mixture was allowed to warm naturally to room temperature and left overnight. To the reaction mixture was added 25 ml of water then 36 ml of 1 N hydrochloric acid. The resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was dried over MgS0 and filtered. The solvent was removed from the filtrate in vacuo to yield 7.00 g (83.4 % of theory) of 2,2-dibromo-1 ,1-dipentyl-cyclopropane as an oil. c. 2-Bromo-1 ,1-dipentyl-cyclopropane To a solution of 4.00 g (0.0118 mol) of 2,2-dibromo-1 ,1 -diperityl- cyclopropane in i 1 ml of methanol was added 0.744 nil ( 0.0129 mol) of glacial c^ 'i^'and O 6f5 -g (6j'oh !iB mol) of zinc dust. After 2 hours 0.744 ml of glacial acetic acid and 0.766 g of zinc diist ere added to the mixture- After 2 further hours; the solvent was removed from the reaction mixture in vacuo. The resulting residue was extracted with hexanes arid then diethyl ether from wateV. he combined organic layers were dried over gSO* and ~ filtered . The solvent was removed from the filtrate //i vacuo to yield 2.1 g (68.2% of theory) of an equal mixture of 2-bromo-1 ,1-dipentyl-cyclopropane and 1 ,1-dipentyl-cyclopropane as an oil. d. 3 -Dipentyl-cydopropene r .

To a solution of 1.90 g of an equal mixture of 2-bromo-1 ,1-dipentyl- cycibpropahe and iVl-dipentyi-c ci propane in 10 ml dimethylsulfoxide was added 0.818 g (0.00308 mol) of potassium t-butoxide. The resulting mixture was eated to 85 °C for 5 hours and then stirred at room temperature for 16 hours. To this was added 0.100 g of potassium t-butoxide. The resulting mixture was heated to 85 CC for 2 hours then cooled to room temperature.

The reaction mixture was poured onto water and then extracted with diethyl ether. The resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was dried over gS04 and filtered. The solvent was removed from the filtrate in vacuo to yield 1.90 g of 3,3-dipentyl-cyclopropene mixed in equal parts with 1 ,1-dipentyl-cyclopropane as an oil.

EXAMPLE 20 Preparation of 1-Pent-2-enyl-2-pentyl-cyclopropene (Compound 17) A solution of 1.00 g (0.00287 mol) of 1 ,1 ,2-tribromo-2-pentyl- cyclopropane in 4 ml of tetrahydrofuran was placed under an inert atmosphere of nitrogen via a Firestone valve. To this mixture, cooling in an ice water bath, was added via syringe 3.58 ml (0.00861 mol) of 1.6 n- butyllithium in hexanes. After 30 minutes, 0.432 ml (0.00287 mol) of tetramethylethylene diamine and 0.339 ml (0.00287. mol) of 1-bromo-2- After 1 hour, 0.478 ml hexamethylphosphoramide and 0.325 ml of 1-bromo-2- pentene were added separately via syringe. The reaction mixture was allowed to warm to room temperature and stirred for 2 days. The reaction was quenched by the addition of 2 ml of water by syringe. This residue was extracted with diethyl ether. The resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was dried over gS04 and filtered. The solvent was removed from the filtrate in vacuo to yield 0.280 g of 1 :1 mixture of 1 -pent-2-enyl-3,3-dipentyl- cyclopropene and 1 ,1-dipentyl-cyclopropane as an oil.

EXAMPLE 22 exane as the eluent. 10 mg sample f 67% pure 1-(oct-7-eny - cyclopropene was obtained.

EXAMPLE 23 Preparation of 4-(1-Cyclopropenyl)-2-methylbutan-2-ol (Compound 20) a. 4-Bromo-pent-4-enoic acid ethyl ester This ester was prepared by the method of Mori, JOC, 1983 48, 4062 b. 3-(1 ,2,2-Tribromo-cyclopropyl)-propionic acid ethyl ester To a solution made of 12.12 g (58 mmol) of 4-bromo-pent-4-enoic acid ethyl ester and 51 g (202 mmol) of bromoform and 100 g of methylene chloride was added 2.0 g of ί, ,-dibenzy^- 1 l ,- tetramethylethylenediammonium dibromide and 27.1 g (218 mmol) of 45% yield 0.380 g of 75% pure with remainder being diethyl ether (79% of theoretical yield corrected for ether) of 4-cycloprop-1-enyl-2-methyl-butan-2-ol as an oil. Product is stored at -80 °C.

EXAMPLE 24 Preparation of Methyl sterculate (Compound 21) Methyl sterculate (40% purity) was formed by the procedure of Gensler et. al. (Gensler, W. J.; Floyd, M. B.; Yanase, R.; Pober, K. W. J. Am.

Chem. Soc, 1970, 92, 2472).

EXAMPLE 25 Preparation of Hex-5-yne 2-octylcycloprop-2-ene-1-carboxylate (Compound 22) a. Ethyl 2-octylcyclpprop-2-ene-1-carpoxylate Ethyl 2-octyicycloprop-2-ene-1-carboxylate was prepared from 1- decyne and ethyl diazoacetate by the method of Mueller, P.; Pautex, N.; Helv. Chim Acta 1990, 73, 1233. c. 2-Octylcycloprop-2-ene-1-carbonyl chloride ^ ^ . >¾., A solution of 2-octylcycloprop-2-ene-1 -carboxylic acid (350 mg, 1,8 mmol) in ether was treated with 0.45 g (3.5 mmol) of oxalyl chloride at room temperature. The reaction mixture was stirred for one hour then stripped to give 330 mg of 2-octylcycloprop-2-ene-1-carbonyl chloride. d. Hex-5-yne 2-octylcycloprop-2-ene-1 -carboxylate To a solution of 2-octylcycloprop-2-ene-1-carbonyl chloride (330 mg, 1.5 mmol) in 5 ml of ether is added 1.5 ml of triethylamine. 5-Hexyn-1-ol (0.18g, 1.8 mmol) was added to the reaction mixture, which was stirred at room temperature over the weekend. Water and additional ether were added, and the resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was washed with water and brine, dried over MgSO^ filtered and stripped. The product was chromatographed on silica gel to give 40 mg of 60% pure hex-5-yne 2- octylcycloprop-2-ene-1 -carboxylate containing roughly 40% 2-octylcycloprop- 2-ene-1-carboxylic acid. 1 ,1 ,2-Trib mo-^ (1.28 g, 3.1 mmol) was dissolved in 60 ml of ether and cooled to -78°C. Methyllithium (9.0 ml, 2.6 mmol) was added and the reaction was stirred at -78°C for two hours. The reaction mixture was put in an ice bath for 5 minutes, then recooled to -78°C until workup. Water was added to the reaction mixture, which was warmed to 5 room temperature. The aqueous phase was separated, and the ether phase was extracted with three times with 1 NaOH solution. The ether phase contained 8-cycloprop-1-enyl-octan-2-one and the combined aqueous extracts contained 7-cycloprop-1 -enyl-heptanoic acid.

The ether phase from above was washed with brine, dried over magnesium sulfate and stripped to give 200 mg of 8-cycloprop-1-enyl-octan- 2-one, Compound 46.

The combined aqueous extracts containing 7-cycloprop-1-enyl-heptanoic acid were acidified with aqueous HCI, and extracted with ether three times.

The ether extracts were washed with brine, dried over magnesium sulfate and 15 stripped to give 300 mg of 7-cycloprop-1-enyl-heptanoic acid, Compound 7.

·.. .. ,·,. ·, -· , E^ PLE 27 . . ... ; Preparation of 8-Cycloprop-1-enyl-octan-2-one O-methyl oxime ' '(Compound 47) EXAMPLE 28 Preparation of 7-Cycloprop-1-enyl-heptanoic acid diethylamide (Compound 48) A solution of 7-cycloprop-1-enyl-heptanoic acid (0.25 g, 1.5 mmol) in 10 ml of ether was cooled in an ice bath and treated with 0.3 mL of triethyl amine. Methyl chloroformate (0.16 g, 17 mmol) was added, and the reaction was stirred for 1.5 hours. Excess diethylamine was added while the reaction was still cooled in an ice bath, and the reaction was stirred for one half hour. Additional ether and water were added, and the aqueous phase was acidified to pH 1 with aqueous HCI. The phases were separated, and the organic phase was washed with water, 1 N sodium hydroxide, water and brine. The . organic phase was dried over magnesium sulfate, filtered and stripped.

Column chromatography gave 70 mg of colorless liquid 7-cycloprop-1-enyi- heptanpip acid diethylamide (Compound 48) in 74% purity.

EXAMPLE 29 In a manner similar to those described above, the following compounds were made: d itional compounds Table 4 NMR Data 1/37663 FCTVUSOO/31944 EXAMPLE 31 Biological Activity Tomato Epinasty Test Protocols The test procedure is designed to determine the ability of an compound according to the present invention to block the epinastic growth response induced by ethylene in tomato plants when the compound is administered either as a volatile gas or as a component of a spray solution.

Treatment chambers are of an appropriate size for the test plants and are airtight. Each is fitted with a reusable septum to be used for injection of ethylene.

Test plants are Patio variety tomato seedlings planted two plants per three inch square plastic pot. sealed chamber. Sixteen hours later the chambers are opened in an exhaust hood, allowed to air and the plants scored visually for the degree of protection against ethylene-induced epinasty conferred by the experimental compound when compared to ethylene treated and untreated controls on a scale of 0 to 10. A rating of 10 means complete protection. A rating of 0 means no protection from the effects of ethylene.

When applied as a spray in the tomato epinasty test, 1-pentylcyclobutene was superior to 1-butylcyclobutene. The pentyl analog was rated 10 (complete protection), while the butyl analog was rated 5.

The activity of the compounds of this invention in the tomato epinasty test when applied as a gas is given in the table.

Table s Activity of compounds according to the present invention in the tomato epinasty test 0 0 8 0 9 5 9 0 9.5 9 9 3.5 3 9.5 • 0 4.5 1Q 4 3 2 0 0 9 3 9.5 7 0 The foregoing embodiments and examples are illustrative of the present invention and are not to be construed as limiting thereof. The invention is defined by the following claims, with equivalents of the claims to be included therein.

Claims

1 . A method of inhibiting an ethylene response in a plant, comprising applying to the plant an effective ethylene response-inhibiting amount of a compound of Formula I : wherein: n is a number from 1 to 4; and each R is independently a saturated or unsaturated, linear or branched-chain, Linsubstituted or substituted, C6 to Cio alkyl, alkenyl, or alkynyl.

2. A method according to Claim 1 , wherein n is 1 or 2.

3. A method according to Claim 1 , wherein n is 1 .

4. A method according to Claim 1 , wherein said applying step is carried out by contacting said plant to a gas of said compound.

5. A method according to Claim 1 , wherein said applying step is carried out by spraying said plant with a solution comprising said compound.

6. A method according to Claim 1 , wherein said apply ing step is carried out by contacting said plant to a solid comprising said compound.

7. A method according to Claim 1 , wherein said ethylene response is fruit ripening.

8. A method according to Claim 1 , wherein said ethylene response is vegetable ripening. 44 149636/2

9. A method according to Claim 1 . wherein said ethylene response is flower senescence.

10. A method according to Claim 1 , wherein at least one R is an alky 1, alkenyl. or alkynyl substituted with at least one substituent selected from the group consisting of halogen, amino, alkoxy, carboxy, alkoxycarbonyl, and hydroxy.

1 1 . A method according to C laim 1 , wherein at least one of the carbon atoms in at least one R group is replaced by at least one constituent selected from the group consisting of ester groups, nitrites, amines, amine salts, acids, acid salts, esters of acids, hydroxy 1 groups, and heteroatoms selected from the group consisting of oxygen and nitrogen.

12. A method according to Claim 3, wherein R is hexyl.

1 3. A method according to Claim 3, wherein R is octyl.

14. A method of inhibiting abscission in a plant, comprising applying to the plant an effective abscission-inhibiting amount of a compound of Formula I: wherein: n is a number from 1 to 4; and each R is independently a saturated or unsaturated, linear or branched-chain, unsubstituted or substituted, C6 to C^ alkyl, alkenyl, or alkynyl.

1 5. A method according to Claim 14, wherein n is 1 or 2.

1 6. A method according to Claim 14, wherein n is 1 .

.1 7. A method according to Claim 14, wherein said applying step is c out by contacting said plant to a gas of said compound. 45 149636/2

1 8. A method according to Claim 14. wherein said applying step is carried out by spraying said plant with a solution comprising said compound.

19. A method according to Claim 14. wherein said applying step is carried out by contacting said plant to a solid comprising said compound.

20. A method according to Claim 14, wherein at least one R is an alky I. alkenvl. or alkynyl substituted with at least one substituent selected from the group consisting of halogen, amino, alkoxy, carboxy, alkoxycarbonyl, and hydroxy .

21 . A method according to Claim 14, wherein at least one of the carbon atoms in at least one R group is replaced by at least one constituent selected from the group consisting of ester groups, nitriles, amines, amine salts, acids, acid salts, esters of acids, hydroxy 1 groups, and heteroatoms selected from the group consisting of oxygen and nitrogen.

22. A method according to Claim 16, wherein R is hexyl.

23. A method according to Claim 16, wherein R is octyl .

24. A method of prolonging the life of a cut flower, comprising applying to the cut flower an effective l i fe-prolonging amount of a compound of Formula I : wherein: n is a number from 1 to 4; and each R is independently a saturated or unsaturated, linear or branched-chain, unsubstituted or substituted, C6 to Cio alkyl, alkenyl, or alkynyl.

25 A method according to Claim 24, wherein n is 1 or 2.

26. A method according to Claim 24. wherein n is 1 46 149636/2

27. A method according to Claim 24, wherein said applying step is carried out by contacting said plant to a gas of said compound.

28. A method according to Claim 24, wherein said applying step is carried out by spraying said plant with a solution comprising said compound.

29. A method according to Claim 24, wherein said applying step is carried out by contacting said plant to a solid comprising said compound.

30. A method according to Claim 24, wherein at least one R is an alky I, alkenyl, or alkyny l substituted with at least one substituent selected from the group consisting of halogen, amino, alkoxy, carboxy, alkoxycarbonyl, and hydroxy.

3 1 . A method according to Claim 24, wherein at least one of the carbon atoms in at least one R group is replaced by at least one constituent selected from the group consisting of ester groups, nitriles, amines, amine salts, acids, acid salts, esters of acids, hydroxyl groups, and heteroatoms selected from the group consisting of oxygen and nitrogen.

32. A method according to Claim 26, wherein R is hexyl.

33. A method according to Claim 26, wherein R is octyl.

34. A method of inhibiting an ethylene response in a plant, comprisi ng apply ing to the plant an effective ethylene response-inhibiting amount of a composition, said composition comprising a compound of Formula I : wherein: n is a number from 1 to 4; and each R is independently a saturated or unsaturated, l inear or branched-chain. unsubstituted or substituted. C(, to C^o alky!. alkenyl, or alkynyl . 47 149636/2

35. A method according to Claim 34. wherein n is 1 or 2.

36. A method according to Claim 34. wherein n is 1 .

37. A method according to Claim 34, wherein said applying step is carried out by contacting said plant to said composition wherein said composition comprises a gas.

38. A method according to Claim 34, wherein said applying step is carried out by spraying said plant with said composition and wherein said composition comprises a solution.

39. A method according to Claim 34, wherein said apply ing step is carried out by contacting said plant to said composition and wherein said composition comprises a solid.

40. A method according to Claim 34, wherein said ethylene response is fruit ripening.

41 . A method according to Claim 34, wherein said ethylene response is vegetable ripening.

42. A method according to Claim 34, wherein said ethylene response is flower senescence.

43. A method according to Claim 34, wherein said composition further comprises an inert carrier.

44. A method according to Claim 34, wherein at least one R is an alky 1, alkenyl. or alkynyl substituted with at least one substituent selected from the group consisting of halogen, amino, alkoxy, carboxy, alkoxycarbonyl, and hydroxy.

45. A method according to C laim 34, wherein at least one of the carbon atoms i n at least one R group is replaced by at least one constituent selected from the 48 149636/2 group consisting of ester groups, nitriles. amines, amine salts, acids, acid salts, esters of acids, hydroxy 1 groups, and heteroatoms selected from the group consisting of oxygen and nitrogen.

46. A method according to Claim 36, wherein R is hexyl.

47. A method according to Claim 36, wherein R is octyl .

48. A method of inhibiting abscission in a plant, comprising applying to the plant an effective abscission-inhibiting amount of a composition, said composition comprising a compound of Formula Γ: wherein: n is a number from 1 to 4; and each R is independently a saturated or unsaturated, linear or branched-chain, unsubstituted or substituted, C6 to C2o alkyl, alkenyl, or alkynyl.

49. A method according to Claim 48, wherein n is 1 or 2.

50. A method according to Claim 48, wherein n is 1 .

5 1 . A method according to Claim 48. wherein said applying step is carried out by contacting said plant to said composition and wherein said composition comprises a gas.

52. A method according to Claim 48, wherein said applying step is carried out by spraying said plant with said composition and wherein said composition comprises a solution.

53. A method according to Claim 48. wherein said applying step is carried out by contacting said plant to said composition and wherein said composition comprises a solid. 49 149636/2

54. A method according to Claim 48, wherein said composition further comprises an inert carrier.

55. A method according to Claim 48, wherein at least one R is an alky 1. alkenyl. or alkynyl substituted with at least one substitueiit selected from the group consisting of halogen, amino, alkoxy, carboxy, alkoxycarbonyl, and hydroxy.

56. A method according to Claim 48, wherein at least one of the carbon atoms in at least one R group is replaced by at least one constituent selected from the group consisting of ester groups, nitriles, amines, amine salts, acids, acid salts, esters of acids, hydroxy 1 groups, and heteroatoms selected from the group consisting of oxygen and nitrogen.

57. A method according to Claim 50, wherein R is hexyl.

58. A method according to Claim 50, wherein R is octyl.

59. A method of prolonging the life of a cut flower, comprising applying to the cut flower an effective life-prolonging amount of a composition, said composition comprising a compound of Formula I : wherein : n is a number from 1 to 4: and each R is independently a saturated or unsaturated, l inear or branched-chain, unsubstituted or substituted, C6 to C2o alkyl, alkenyl, or alkynyl.

60. A method according to Claim 59, wherein n is 1 or 2.

61 A method according to Claim 59, wherein n is 1 50 149636/2

62. A method according to Claim 59, wherein said applying step is carried out by contacting said plant to said composition and wherein said composition comprises a gas.

63. A method according to Claim 59. wherein said apply ing step is carried out by spraying said plant with said composition and wherein said composition comprises a solution.

64. A method according to Claim 59, wherein said applying step is carried out by contacting said plant to said composition and wherein said composition comprises a solid.

65. A method according to Claim 59, wherein said composition further comprises an inert carrier.

66. A method according to Claim 59, wherein at least one R is an alky 1, alkenyl, or alkynyl substituted with at least one substituent selected from the group consisting of halogen, amino, alkoxy, carboxy, alkoxycarbonyl, and hydroxy.

67. A method according to Claim 59, wherein at least one of the carbon atoms in at least one R group is replaced by at least one constituent selected from the group consisting of ester groups, nitriles. amines, amine salts, acids, acid salts, esters of acids, hydroxy 1 groups, and heteroatoms selected from the group consisting of oxygen and nitrogen.

68. A method according to Claim 61 , wherein R is hexyl .

69. A method according to C laim 61 , wherein R is octyl . For the Applicant